Nanotechnology may turn stem cells into breast-cancer smart bombs

Triple-negative breast cancer is, in a way, the outlier in breast cancer research. Increasingly effective targeted treatments are now used against other breast cancers, but with no vulnerable gene target, no response to hormone therapy and a resistance to most available standard treatments, triple-negative breast cancer can be a monstrous mountain to overcome.

City of Hope researchers Karen Aboody, M.D., and Jacob Berlin, Ph.D., are collaborating to develop new therapies using neural stem cells and nanoparticles. Ultimately, such treatments may offer more options and improved treatments for women with triple-negative breast cancer — so-called because it isn’t fueled by the hormones estrogen or progesterone or by too many HER2 receptors.

"Neural stem cells are tumor-tropic, meaning they naturally migrate to tumors," Aboody, an associate professor in the Department of Neurosciences, said in a statement. "We're currently conducting a clinical trial of a neural stem cell-based treatment for brain tumors, and are investigating treatment of other types of cancer."

The Mary Kay Foundation recently awarded Aboody and Berlin a $100,000 grant to support their laboratory research. In 2012, the foundation awarded $100,000 grants each to 13 projects across the U.S. for scientists conducting cutting-edge research.

Aboody has worked with neural stem cells from early in her career and, contrary to many expert opinions at the time, proved that neural stem cells traveled through the body to tumor sites.

Neural stem cells give rise to additional neural stem cells and all the neurons, astrocytes and oligodendrocytes that make up the central nervous system.

In her current research on triple negative breast cancer, she’ll engineer stem cells to carry a nontoxic compound that will convert into a highly toxic drug that kills cancer cells only when mixed with a specific second nontoxic compound. Because the neural stem cells will be clustered around the tumors, the two compounds will only mix and convert into the toxic drug at the tumor site — instead of circulating through healthy parts of the body, as is typical for most chemotherapy treatments.

“The stem cells can also be loaded with nanoparticles,” said Berlin, assistant professor, Department of Molecular Medicine, Beckman Research Institute of City of Hope. “In this case, once the stem cells transport the nanoparticles to the tumor, a mild laser can be applied to the area and it will cause the nanoparticles to heat up and destroy the tumor.”

Nanoparticles are molecules built up of specific atoms. Generally, they are about 10,000 times smaller than the width of a human hair.

Aboody's platform of using neural stem cells has already been validated for glioblastoma, a rapid-growing type of brain tumor, and has a clinical trial currently enrolling patients. She will have to conduct the same laboratory studies to validate the use of different attachments to the stem cells and their use in different types of cancers. Both the two-compound approach and the nanoparticle approach will target treatment to the cancer cells, while sparing healthy cells.

Said Aboody and Berlin in a joint statement: “This research will serve as the foundation for translational studies — potentially resulting in improved clinical outcome within the next decade for triple-negative breast cancer patients.”